LEE011 is a new oral drug designed to inhibit the activity of an enzyme known as CDK4/6. CDK4/6 is involved in the process that allows both normal and cancer cells to divide and multiply. Cancer cells are often driven to divide and multiply by abnormalities that increase the activity of CDK4. Hence there is hope that blocking the activity of CDK4 may slow the growth of some cancers. LEE011 has shown anti-cancer activity in several different tumor models in animals.

Because CDK4 is important in both normal and cancerous cells, LEE011 is expected to decrease the ability of the bone marrow to make white blood cells, platelets, and red blood cells. Although these effects are expected to be reversible, they can increase the risk of infection, bleeding and fatigue.

The primary purpose of this study is to find the highest dose of LEE011 that can be safely given to adult patients with advanced solid tumors or lymphomas for which no further effective standard treatment is available. It will provide information about the side effects that may occur following treatment. The study will also possibly provide early evidence for LEE011's anti-tumor activity.

Any pharmacodynamic activity of LEE011 treatment, as assessed by changes from baseline in biomarkers associated with the pharmacologic activity of LEE011 [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Patients aged ≥18 years with a histologically or cytologically confirmed diagnosis of a solid tumor or lymphoma for which no further effective standard treatment is available

Patients must have an ECOG performance status of 0 - 1

Patients enrolled in the dose expansion phase must have at least one measurable lesion as defined by RECIST criteria for solid tumors or Measurable nodal disease at baseline as defined by Cheson criteria for Lymphoma.

A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies and major surgery) and enrollment in this study, to allow the effects of prior therapy to have abated:

Cytotoxic chemotherapy: ≥ the duration of the cycle of the most recent treatment regimen (a minimum of 2 weeks for all regimens, except 6 weeks for nitrosoureas and mitomycin-C).

Biologic therapy (e.g., antibodies): ≥ 4 weeks.

Patients must have adequate organ function, as defined by the following parameters:

Patients with primary central nervous system tumors or brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of 3 months demonstrates the disease to be stable and if the patient remains asymptomatic, then the patient may be enrolled. Such patients must have no need for treatment with steroids or anti-epileptic medications.

Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 such as patients with a history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastroparesis, unresolved nausea, vomiting, or diarrhea of CTCAE grade > 1

Prior hematopoietic stem cell or bone marrow transplantation

Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

LVEF <45% as determined by MUGA or echo

Complete left bundle branch block

Obligate use of a cardiac pacemaker or implantable cardioverter defibrillator

Congenital long QT syndrome or family history of unexpected sudden cardiac death

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01237236